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May 29, 2012

Adherence Challenges in Intermittent HIV PrEP Study

by Tim Horn

Intermittent use of Truvada (tenofovir plus emtricitabine) as pre-exposure prophylaxis was associated with poor adherence, compared with daily use of the tablet to prevent HIV infection, according to results of a small clinical trial published in the online scientific journal PLoS ONE.

Using electronic pill caps, the Kenyan study found that the adherence rate associated with daily PrEP use was 83 percent. Among those using intermittent therapy—Truvada taken on Monday, Friday and within two hours following sexual intercourse—the adherence rate was 55 percent. Among those who only took Truvada within two hours following sexual intercourse, the post-coital adherence rate was only 26 percent.

Truvada as PrEP was recently recommended for U.S. Food and Drug Administration (FDA) approval by the Antiviral Drugs Advisory Committee. The recommendation is based on data from several clinical trials, all exploring the safety and efficacy of Truvada PrEP used daily.

There has been interest in exploring alternative dosing strategies, notably scheduled and as-needed intermittent use of the drug. Experts hypothesize less frequent dosing may reduce the risk of side effects and prove easier for people to use, in light of the poor adherence that has been noted in clinical trials evaluating daily use of Truvada.

Preliminary results from a study involving 67 African men who have sex with men (MSM) and five female sex workers were reported at the International AIDS Conference. The final study report was authored by Gaudensia Mutua, MD, of the Kenya AIDS Vaccine Initiative and her colleagues and published by PLoS ONE in April.

The intermittent PrEP strategies appeared to be safe and well tolerated. Ninety-seven percent of the side effects reported were mild to moderate in severity, and 91 percent were judged by the researchers to be unrelated to the use of Truvada.

Mild creatinine elevations—a possible sign of Truvada kidney toxicity—were documented in three study volunteers receiving the drug, though all resolved spontaneously over the duration of the study. Two cases of abnormal creatinine clearance, another potential sign of Truvada-related kidney impairment, were reported in one Truvada-treated study volunteer and one placebo-treated study volunteer. These irregularities also resolved spontaneously, and no other clinically significant signs of kidney dysfunction were documented.

One HIV infection occurred in a volunteer in the placebo group at week 16.

Adherence to the study drug regimens in this trial was measured using the medication event monitoring system (MEMS)—electronic pill caps that record each instance in which the pill container is opened—as well as monthly follow-up interviews.

Daily text messages were used to collect data on sexual behavior in order to estimate post-intercourse PrEP adherence. “The lower adherence rate to the post-coital doses in the intermittent regimen suggests that post-coital dosing may be challenging in the populations included in this trial,” explains the International AIDS Vaccine Initiative (IAVI), a developer of the study, in a news announcement. “However it may also reflect difficulties in accurately measuring post-coital dosing using MEMS or self-report data.

“Further study will be needed to determine whether the intermittent use of Truvada as pre-exposure prophylaxis will be a viable HIV-prevention strategy for MSM and female sex workers in Africa,” IAVI suggests. “Currently, few studies address adherence to non-daily medication regimens, and these findings will be useful to future studies examining the intermittent use of PrEP for HIV prevention.”

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